Does treatment with selinexor, bortezomib and dexamethasone improve the outcome of patients with multiple myeloma?

This study investigated if giving patients with aggressive multiple myeloma (MM) a combination of selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (Ozurdex) could improve their survival. The study suggested that this combination improved patients’ outcomes.

Multiple Myeloma (MM) is an aggressive type of blood cancer. One standard treatment for MM is bortezomib plus dexamethasone (Vd). However, patients can experience high levels of side effects such as nerve damage linked to bortezomib treatment. A high number of patients with MM are resistant to therapy.

Exportin-1 (XPO1) is a protein that promotes tumor growth and survival. It is found at high levels in patients that have more aggressive MM. These patients often develop resistance to bortezomib. Selinexor prevents the activity of XPO1. The use of selinexor with dexamethasone for patients with resistant MM is approved in the USA. However, it is not known if the combination of selinexor with Vd could be effective in improving the survival of patients with MM that has become resistant to therapy.

402 patients with resistant MM were enrolled in this trial. Patients had previously received up to 3 types of treatment. Patients were randomly split into two groups. 195 (49%) patients were given selinexor in combination with Vd (group 1). 207 (51%) patients were given Vd alone (group 2). The average follow-up time was 13.2 months for group 1 and 16.5 months for group 2.

Patients in group 1 had a 30% longer survival time without the disease progressing (13.93 months) compared to those in group 2 (9.46 months). More patients in group 1 responded to treatment (76.4%) compared to group 2 (62.3%).

The most common severe side effects were low levels of platelets (blood cells involved in clotting; 39% in group 1 vs 17% in group 2), anemia (16% in group 1 vs 10% in group 2), and low levels of white blood cells that fight off infections (9% in group 1 vs 3% in group 2). Nerve damage is one of the main side effects of bortezomib treatment. Patients in group 1 were 48% less likely to experience nerve damage compared to group 2. 

This study showed that treatment of MM with Vd + selinexor improved the survival of patients without the disease progressing compared to Vd alone.

The study did not investigate the level of XPO1 in these patients. Knowledge about XPO1 levels could have helped to identify patients who would respond best to Vd+ selinexor. The study was funded by Karyopharm Therapeutics who manufacture selinexor.